AbstractBackground and Purpose: Onychomycosis is fungal infection of the nails with an overall increasing incidence, worldwide. The epidemiological aspects of onychomycosis in Khuzestan, Iran have not been established. This study was aimed to evaluate the clinical and mycological status of fungal nail infection in Khuzestan Province, Iran.Material and Methods: The study population included 433 patients (143 males vs. 290 females). Nail samples were undergone to primary direct microscopy and culture. The isolated yeasts and dermatophytes were then subjected to additional molecular identification by r-DNA ITS-RFLP. Identification of some non-dermatophytes molds (NDMs) and unknown yeasts were accomplished by ITS and beta tubulin sequencing.Results: Onychomycosis was confirmed in 154 patients (35.6%; 58 males vs. 96 females) whose age ranged from 2-85 years with highest prevalence in the age group of 41-50 years old. Infection was more occurred due to yeasts (59.7%) with Candida albicans as the most frequent (29.35%) species, followed by C. parapsilosis (13.8%) and C. tropicalis (4.5%). Dermatophytes were isolated in 38.35% of the cases; the most commonly isolates were found to be Trichophyton interdigitale (21.1%), Epidermophyton floccosum (10.5%), T. rubrum (5.25%) and Microsporum canis (1.5%). NDMs were isolated only in 4.5% with Aspergillus spp., as the commonest agents. Dermatophytes and NDMs more frequently seen in toenails whereas, yeasts mostly infected fingernails and fingernail onychomycosis has remarkably more occurred in females than males (P < 0.05).Conclusion: The study highlighted that the agents of infection in the population with onychomycosis from Khuzestan have shifted from dermatophytes to the yeasts.